This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ultimate objective of this project is to develop a gene therapy protocol that will be safe for use in humans and will reverse diabetes and either eliminate or significantly reduce the dependence on insulin for treatment of diabetes. This project will use baboons as they most closely resemble human physiology and would best replicate the therapeutic efficacy and potential toxicities that would be seen in human subjects in the future. It will compare the toxicity and duration and level of expression of viruses containing human genes and evaluate their therapeutic efficacy in inducing new insulin producing islet formation in the livers of the treated diabetic subjects. Finally, we will compare the response in terms of freedom from insulin requirement, ability to produce insulin from the new islets generated in the liver, and the duration of this response.